+
Open data
-
Basic information
Entry | Database: PDB / ID: 7dxk | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Human 128QHuntingtin-HAP40 complex structure | |||||||||||||||
![]() |
| |||||||||||||||
![]() | STRUCTURAL PROTEIN / Huntingtin / 128Q / HAP40 | |||||||||||||||
Function / homology | ![]() vesicle cytoskeletal trafficking / regulation of cAMP-dependent protein kinase activity / : / positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity / microtubule-based transport / vocal learning / regulation of CAMKK-AMPK signaling cascade / negative regulation of proteasomal protein catabolic process / positive regulation of mitophagy / profilin binding ...vesicle cytoskeletal trafficking / regulation of cAMP-dependent protein kinase activity / : / positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity / microtubule-based transport / vocal learning / regulation of CAMKK-AMPK signaling cascade / negative regulation of proteasomal protein catabolic process / positive regulation of mitophagy / profilin binding / vesicle transport along microtubule / positive regulation of cilium assembly / retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum / presynaptic cytosol / positive regulation of aggrephagy / positive regulation of lipophagy / dynein intermediate chain binding / postsynaptic cytosol / beta-tubulin binding / Golgi organization / establishment of mitotic spindle orientation / dynactin binding / Regulation of MECP2 expression and activity / autophagosome / inclusion body / heat shock protein binding / centriole / negative regulation of extrinsic apoptotic signaling pathway / kinase binding / protein destabilization / cytoplasmic vesicle membrane / p53 binding / late endosome / transmembrane transporter binding / early endosome / nuclear body / positive regulation of apoptotic process / axon / dendrite / apoptotic process / perinuclear region of cytoplasm / Golgi apparatus / endoplasmic reticulum / protein-containing complex / nucleoplasm / identical protein binding / nucleus / cytoplasm / cytosol Similarity search - Function | |||||||||||||||
Biological species | ![]() synthetic construct (others) | |||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 4.1 Å | |||||||||||||||
![]() | Guo, Q. / Fernandez-Busnadiego, R. | |||||||||||||||
Funding support | ![]()
| |||||||||||||||
![]() | ![]() Title: Pathological polyQ expansion does not alter the conformation of the Huntingtin-HAP40 complex. Authors: Bin Huang / Qiang Guo / Marie L Niedermeier / Jingdong Cheng / Tatjana Engler / Melanie Maurer / Alexander Pautsch / Wolfgang Baumeister / Florian Stengel / Stefan Kochanek / Rubén Fernández-Busnadiego / ![]() ![]() Abstract: The abnormal amplification of a CAG repeat in the gene coding for huntingtin (HTT) leads to Huntington's disease (HD). At the protein level, this translates into the expansion of a polyglutamine ...The abnormal amplification of a CAG repeat in the gene coding for huntingtin (HTT) leads to Huntington's disease (HD). At the protein level, this translates into the expansion of a polyglutamine (polyQ) stretch located at the HTT N terminus, which renders HTT aggregation prone by unknown mechanisms. Here we investigated the effects of polyQ expansion on HTT in a complex with its stabilizing interaction partner huntingtin-associated protein 40 (HAP40). Surprisingly, our comprehensive biophysical, crosslinking mass spectrometry and cryo-EM experiments revealed no major differences in the conformation of HTT-HAP40 complexes of various polyQ length, including 17QHTT-HAP40 (wild type), 46QHTT-HAP40 (typical polyQ length in HD patients), and 128QHTT-HAP40 (extreme polyQ length). Thus, HTT polyQ expansion does not alter the global conformation of HTT when associated with HAP40. | |||||||||||||||
History |
|
-
Structure visualization
Movie |
![]() |
---|---|
Structure viewer | Molecule: ![]() ![]() |
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 477.8 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 381 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 30912MC ![]() 7dxjC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 361698.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Details: 128Q-Huntingtin Source: (gene. exp.) ![]() Gene: HTT, HD, IT15 / Production host: ![]() ![]() |
---|---|
#2: Protein | Mass: 39141.879 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: Human 128QHuntingtin-HAP40 complex structure / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: GOLD / Grid type: Quantifoil |
Vitrification | Cryogen name: ETHANE-PROPANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-
Processing
EM software |
| |||||||||
---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||
3D reconstruction | Resolution: 4.1 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 122992 / Symmetry type: POINT |